NM_005760.3:c.2847A>C

Variant names:

• chr2-37211036-T-G
• NM_005760.3:c.2847A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005760.3(CEBPZ):​c.2847A>C​(p.Lys949Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K949E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEBPZ NM_005760.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.581
• Publications: 0 publications found

Genes affected

CEBPZ (HGNC:24218): (CCAAT enhancer binding protein zeta) This gene belongs to the CBF/Mak21 family. The encoded protein plays a role in cellular response to environmental stimuli through a transcriptional process that involves heat shock factors, conserved DNA elements (heat shock elements or HSEs) and CCAAT boxes. The protein acts as a DNA-binding transcriptional activator and regulates the heat-shock protein 70 (HSP70) promoter in a CCAAT-dependent manner. The protein is also involved in cell growth and differentiation, particularly, hematopoietic differentiation. [provided by RefSeq, Nov 2020]

CEBPZOS (HGNC:49288): (CEBPZ opposite strand) Predicted to be located in mitochondrial membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272054 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1393035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005760.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPZ	NM_005760.3	MANE Select	c.2847A>C	p.Lys949Asn	missense	Exon 13 of 16	NP_005751.2
	CEBPZOS	NR_136316.2		n.469-2401T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPZ	ENST00000234170.10	TSL:1 MANE Select	c.2847A>C	p.Lys949Asn	missense	Exon 13 of 16	ENSP00000234170.5	Q03701
	CEBPZ	ENST00000898579.1		c.2847A>C	p.Lys949Asn	missense	Exon 13 of 16	ENSP00000568638.1
	CEBPZ	ENST00000938546.1		c.2844A>C	p.Lys948Asn	missense	Exon 13 of 16	ENSP00000608605.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.0048
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.58
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.083
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.088	T
Polyphen		0.94	P
Vest4		0.20
MutPred		0.19		Gain of ubiquitination at K945 (P = 0.0325)
MVP		0.42
MPC		0.094
ClinPred		0.97	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.17
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-37438179;